Is fasting leptin associated with insulin resistance among nondiabetic individuals? The Miami Community Health Study

OBJECTIVE - Whether serum leptin levels are associated with insulin resista nce independent of the effects of hyperinsulinemia and adiposity is an impo rtant unanswered question. We examined the relationship between the rate of insulin-mediated glucose uptake and serum leptin concentrations among nond iabetic men and women. RESEARCH DESIGN AND METHODS - A cross-sectional analysis was performed amon g 49 young to middle-aged men and women who participated in the Miami Commu nity Health Study. All participants had measures of insulin resistance (eug lycemic-hyperinsulinemic clamp), postchallenge insulin levels, fasting seru m leptin levels, and several measures of adiposity. RESULTS - The rate of insulin-mediated glucose uptake (M in milligrams per kilogram per minute) was significantly associated with leptin concentration s in both men (r = -0.83; P < 0.001) and women (r = -0.59; P < 0.001). M wa s also inversely related to percent body fat and to the 2-h insulin area un der the curve (AUC). After covariate adjustment for sex, percent body fat, and AUG, leptin remained a significant correlate of M (P = 0.04). CONCLUSIONS - Cross-sectionally leptin was significantly associated with in sulin resistance in this nondiabetic sample of men and women. There may be a different physiological mechanism to explain the leptin/insulin resistanc e association apart from the insulin/adiposity link. Confirmatory evidence awaits the results of clinical trials.